Ultrasensitive photoelectrochemical biosensor for DNA 5-methylcytosine analysis based on co-sensitization strategy combined with bridged DNA nanoprobe

Altered DNA methylation in the form of 5-methylcytosine (5-mC) patterns is correlated with disease diagnosis, prognosis, and treatment response. Therefore, accurate analysis of 5-mC is of great significance for the diagnosis of diseases. Here, an efficient enhanced photoelectrochemical (PEC) biosensor was designed for the quantitative analysis of DNA 5-mC based on a cascaded energy level aligned co-sensitization strategy coupling with the bridged DNA nanoprobe (BDN). Firstly, Au nanoparticle/graphite phase carbon nitride/titanium dioxide (AuNPs/g-C 3 N 4 @TiO 2 ) nanocomposite was synthesized through in situ growth of AuNPs on g-C 3 N 4 @TiO 2 surface as a matrix to provide a stable background signal. Next, BDN with a high mass transfer rate synthesized from a pair of DNA tetrahedral as nanomechanical handles was used as a capture probe to bind to the target sequence. The polydopamine nanosphere was applied to load with CdTe QDs (PDANS-CdTe QDs) as a photocurrent label of 5-mC antibodies. When the 5-mC existed, a large number of PDANS-Ab-CdTe QDs were introduced to the electrode surface, the formed CdTe QDs/AuNPs/g-C 3 N 4 @TiO 2 co-sensitive structure could effectively enhance the electron transfer capability and photocurrent response rate due to the effective cascade energy level arrangement, leading to a significantly enhanced photocurrent signal. The proposed PEC biosensor manifested a wide range from 10 −17  M to 10 −7  M and a detection limit of 2.2 aM. Meanwhile, the excellent performance indicated the practicability of the designed strategy, thus being capable of the clinical diagnosis of 5-mC.